Table 4: Antidepressants and Anticonvulsant Medications for the Treatment of Neuropathic Pain Syndromes Antidepressant Medications Formulations Usual Daily Dosage for Neuropathic Pain
FDA-Approved Indications
Venlafaxine (Effexor, generics)
25, 37.5, 50, 75, 100 mg tablets 37.5, 75, 150 mg ER tablets and ER capsules 225 mg ER tablets
75 mg once to tid ER: 75-150 mg once
Depression Generalized anxiety disorder Panic disorder Social anxiety disorder FDA-Approved Indications Bipolar disorder Epilepsy Trigeminal or glossopharyngeal neuralgia
Anticonvulsant Medications
Formulations
Usual Daily Dosage for Neuropathic Pain 400-800 mg divided bid ER: 400-800 mg divided bid
Carbamazepine (Tegretol, generics)
200 mg tablets 100 mg chewable tablets 100, 200, 400 mg ER tablets 100, 200, 300 mg ER capsules 20 mg/mL oral solution 100, 300, 400 mg capsules 600, 800 mg tablets 300, 600 mg ER tablets 50 mg/mL oral solution 150, 300, 600 mg tablets 150, 300, 600 mg ER tablets 60 mg/mL oral solution 25, 50, 75, 100, 150, 200, 225, 300 mg capsules 20 mg/mL oral solution
Gabapentin (Neurontin, generics)
1,800-3,600 mg divided tid ER: 1,800 mg once
Epilepsy Postherpetic neuralgia Trigeminal neuralgia
Oxcarbazepine (Trileptal, generics)
600-1,200 mg divided bid ER: 600-2,400 mg once
Epilepsy
Pregabalin (Lyrica)
150-600 mg divided bid or tid Epilepsy
Fibromyalgia Neuropathic pain Postherpetic neuralgia
ER = extended-release. Note . Adapted from “Algorithm for Neuropathic Pain Treatment: An Evidence-Based Proposal,” by N. B. Finnerup, M. Otto, H. J. McQuay, T. S. Jensen, & S. H. Sindrup, 2005, Pain, 118(3), 289-305, and “PEER simplified decision aid: neuropathic pain treatment options in primary care, ”by K. Chan, D. Perry, A.J. Lindblad, S. Garrison, J. Falk, J. McCormack, C.S. Korownyk, J. Kirkwood, J. Ton, B. Thomas, S. Moe, N. Dugré, M.R. Kolber & G.M. Allanm 2021, Canadian Family Physician, 67 (5), 347-349. Classic cranial neuralgias
Carbamazepine is FDA-approved for the treatment of pain resulting from trigeminal neuralgia. Oxcarbazepine, which is related to carbamazepine, has been shown to provide similar analgesia and may have fewer adverse effects. Ziconotide, a synthetic neuronal N-type calcium channel blocker, is administered intrathecally via a programmable microinfusion device for treatment of severe chronic pain (Wie & Derian, 2021). The drug has been effective, both as monotherapy and when added to standard therapy, for treatment of refractory severe chronic pain, including neuropathic pain. Severe psychiatric effects (paranoid reactions, psychosis) and central nervous system toxicity (confusion, somnolence, unresponsiveness) can occur. Unlike opioids, ziconotide does not cause tolerance, dependence, or respiratory depression and is not a controlled substance (Pope & Deer, 2013; Bäckryd, 2018). Gabapentin is also FDA-approved for treatment of pain resulting from trigeminal neuralgia, and several studies have shown that taking lower doses of gabapentin and morphine together provided better analgesia than taking either drug alone for trigeminal neuralgias (Chaparro, Wiffen, Moore, & Gilron, 2012; Serrano Afonso, Carnaval & Videla Cés, 2021). Pregabalin, which is similar in structure to gabapentin, is approved for treatment of neuropathic pain associated with postherpetic neuralgia, diabetic peripheral neuropathy, and fibromyalgia. The dose of Primary stomatodynia Burning mouth syndrome (stomatodynia) is associated with changes of a neuropathic nature, the main location of which – peripheral or central – remains unknown (Orliaguet & Misery,
pregabalin can be titrated more rapidly than that of gabapentin, but because of some reports of euphoria, pregabalin is classified as a Schedule V controlled substance (Häuser, Bernardy, Uçeyler, & Sommer, 2009). While they are not first-line treatment, the tricyclic antidepressants (TCAs) such as amitriptyline, nortriptyline, and imipramine can relieve many types of neuropathic pain, including diabetic neuropathy, postherpetic neuralgia, polyneuropathy, fibromyalgia, and nerve injury – although these are primarily off- label indications. The analgesic effects of these drugs are likely due to their inhibition of norepinephrine and serotonin reuptake; their antagonism of cholinergic and histaminergic systems causes sedation, urinary retention, and hypotension. Selective serotonin reuptake inhibitors (SSRIs) appear to be less effective than tricyclic antidepressants for treatment of neuropathic pain (Mercier et al., 2013; Szok, Tajti, Nyári & Vécsei, 2019). Venlafaxine is a selective serotonin and noradrenaline reuptake inhibitor (SNRI) and has also been shown to be effective for certain patients suffering from classic cranial neuralgias (Aiyer, Barkin, & Bhatia, 2017). The SSRIs, such as paroxetine and fluoxetine, although as effective as other antidepressants for depression, do not possess analgesic properties (Patel, 2013). Referral of these patients to a neurologist for long-term management may be appropriate in some cases.
2021). Prior to making the diagnosis, it is important to rule out oral mucosal diseases, such as herpes simplex, fungal infections, erosive lichen planus, and aphthous stomatitis (Zakrzewska,
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